The effect of antacids on the occurrence of bile acid and aspirin-induced gastric lesions in rats.
Taurodeoxycholic acid increases the incidence of aspirin induced gastric bleeding in rats and in vitro is well bound by Aludrox (aluminium hydroxide) and poorly bound by Maalox (aluminium hydroxide and magnesium hydroxide). We studied the relevance of this binding, as demonstrated in vitro, by observing the effect of the antacids on the occurrence of taurodeoxycholic acid and aspirin-induced bleeding in vivo in rats. Six groups of fasting male Sprague-Dawley rats (n = 24) were intubated and given either water, Aludrox or Maalox and, 30 min later, aspirin or aspirin plus taurodeoxycholic acid. 4 h later the stomachs were examined and rats were scored positive if a lesion greater than 1 mm across was found (incidence of bleeding); a lesion scoring system was also used (severity of bleeding). The incidence of bleeding was increased from 63% with aspirin to 92% with aspirin plus taurodeoxycholic acid (P less than 0.05). The incidence was reduced to 33% and 67% respectively by Aludrox and to 29% (P less than 0.05) and 71% by Maalox. The severity of bleeding (median lesion score, quartiles in parentheses) was increased from 3 (1;6.5) (aspirin) to 10.5 (6;15) (aspirin plus taurodeoxycholic acid); P less than 0.001. These were reduced to 0.5 (0;3); P less than 0.02 and 5 (0.5;9.5); P less than 0.05 respectively by Aludrox and to 0 (0;3); P less than 0.02 and 3 (2;8); P less than 0.02 by Maalox. The severity of bleeding was reduced by both antacids but the effect appeared to be mainly on the aspirin rather than the bile acid component of the damage.
D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000863:Antacids / Q000494:pharmacology*; D001241:Aspirin / Q000009:adverse effects*; D001647:Bile Acids and Salts / Q000378:metabolism; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D004338:Drug Combinations / Q000494:pharmacology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control; D008276:Magnesium Hydroxide / Q000494:pharmacology; D008297:Male; D051381:Rats; D013270:Stomach / Q000187:drug effects*; D013657:Taurodeoxycholic Acid / Q000009:adverse effects*
D000863:Antacids; D001647:Bile Acids and Salts; D004338:Drug Combinations; D003840:Deoxycholic Acid; C013591:aluminum hydroxide, magnesium hydroxide, drug combination; D013657:Taurodeoxycholic Acid; D000536:Aluminum Hydroxide; D008276:Magnesium Hydroxide; D001241:Aspirin